1)We investigated the therapeutic effect of FK506 on collagen-induced arthritis in rats. It was demonstrated that a single administration of FK506 at a dose of 10 mg/kg on day 12 or 15, after the clinical onset of arthritis was effective in suppressing the severity of arthritis and immune response to type II collagen. In an attempt to gain further insight into the action of FK50l, we also investigated the effect of FK506, in comparison with cyclosporin A, on the development of passive arthritis induced by anti-type II collagen antisera in rats. FK506 pretreatment shortly before serum transfer markedly suppressed the incidence and the severity of passive arthritis, while cyclosporin A pretreatment had no observable effects on this disease when used in doses sufficient to suppress the development of active arthritis induced by collagen immunization. FK506 can act on antibody-mediated effector phase of arthritis and may offer new insights into the possible role of potential therapeutic ut
… Moreility in human autoimmune diseases.2)Treatment of rats with intravenous injection of l ma of soluble native type II collagen induced resistance against the subsequent induction of passive arthritis with anti-type II collagen antisera. However, pretreatment of rats with 20 mg/kg of cyclophosphamide, an agent reputed to damage suppressor T cell function, 2 days before intravenous injection of type II collagen abrogated the antigen-induced resistance against the subsequent induction of passive arthritis. These results provided evidence that antigen-induced resistance to passive arthritis was mediated, at least in part, under the control of cyclophosphamide-sensitive events.3)The role of neutrophils in the induction of passive arthritis with anti-type II collagen antisera was investigated. In cyclophosphamide-induced neutropenic rats, swelling and inflammation associated with the arthritic response were significantly reduced. Administration of 250 mug/kg of granulocyte colony-stimulating factor(G-CSF)to neutropenic rats for 7 consecutive days from the day after cyclophosphamide injection resulted in the recovery of peripheral blood neutrophil count and the significant increase of the incidence and the severity of passive arthritis. Further study demonstrated that a prior administration of 250 mug/kg of G-CSF to naive rats for 3 consecutive days resulted in the significant enhancement of passive arthritis. It was suggested that neutrophils played an important role in the induction of passive arthritis. Less